Enhanced L1CAM expression on pancreatic tumor endothelium mediates selective tumor cell transmigration.
L1 cell adhesion molecule (L1CAM) is a transmembrane cell adhesion molecule initially defined as a promigratory molecule in the developing nervous system that appears to be also expressed in some endothelial cells. However, little is known about the functional role of L1CAM on endothelial cells. We observed that L1CAM expression was selectively enhanced on endothelium associated with pancreatic adenocarcinoma in situ and on cultured pancreatic tumor-derived endothelial cells in vitro. L1CAM expression of endothelial cells could be augmented by incubation with immunomodulatory cytokines such as tumor necrosis factor alpha, interferon gamma, or transforming growth factor beta 1. Antibodies to L1CAM and the respective ligand neuropilin-1 blocked tube formation and stromal cell-derived factor 1beta induced transmigration of tumor endothelial cells in vitro. L1CAM expression on tumor-derived-endothelial cells enhanced Panc1 carcinoma cell adhesion to endothelial cell monolayers and transendothelial migration. Our data demonstrate a functional role of L1CAM expression on tumor endothelium that could favor metastasis and angiogenesis during tumor progression.
Issa
Yasmin
Y
Tumor Immunology Programme, D015, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Nummer
Daniel
D
Seibel
Tobias
T
Müerköster
Susanne Sebens
SS
Koch
Moritz
M
Schmitz-Winnenthal
Friedrich-Hubertus
FH
Galindo
Luis
L
Weitz
Juergen
J
Beckhove
Philipp
P
Altevogt
Peter
P
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D002465:Cell Movement; D016207:Cytokines / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis*; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D016207:Cytokines; D009363:Neoplasm Proteins; D039842:Neural Cell Adhesion Molecule L1; D039942:Neuropilin-1